Submitted on May 10, 2006
Accepted on August 24, 2006
Effects of a Cannabinoid Agonist on Spinal Nociceptive Neurons
in a Rodent Model of Neuropathic Pain
Cheng Liu1 and J. Michael Walker2
1 Psychology, Brown University, Providence, Rhode Island, United States
2 Psychology, Indiana University, Bloomington, Indiana, United States; Psychology and Neuroscience, Brown University, Providence, Rhode Island, United States
The effects of the synthetic cannabinoid WIN 55,212-2 on heat-evoked firing of spinal wide dynamic range (WDR) neurons were examined in a rodent model of neuropathic pain. Fifty-eight WDR neurons (1 cell/animal) were recorded from the ipsilateral spinal dorsal horns of rats with chronic constriction injury (CCI) and sham-operated controls. Relative to sham-operated controls, neurons recorded in CCI rats showed elevations in spontaneous firing, noxious heat-evoked responses, and after discharge firing as well as increases in receptive field size. WIN 55,212-2 (0.0625 mg/kg, 0.125 mg/kg, 0.25 mg/kg, i.v.) dose-dependently suppressed heat-evoked activity and decreased the receptive field areas of dorsal horn WDR neurons in both nerve injured and control rats with a greater inhibition in CCI rats. At the dose of 0.125 mg/kg, i.v., WIN 55,212-2 reversed the hyperalgesia produced by nerve injury. The effect of i.v. administration of WIN 55,212-2 appears to be centrally mediated because administration of the drug directly to the ligated nerve did not suppress the heat-evoked neuronal activity in CCI rats. Pretreatment with the cannabinoid CB1 receptor antagonists SR141716A or AM251, but not the CB2 antagonist SR144528, blocked the effects. These results provide a neural basis for reports of potent suppression by cannabinoids of the abnormal sensory responses that result from nerve injury.
